Molecular and Cellular Biochemistry

, Volume 197, Issue 1–2, pp 129–135

The protein kinase inhibitor, H-7, suppresses heat-induced activation of heat shock transcription factor 1

  • Ken Ohnishi
  • Xinjiang Wang
  • Akihisa Takahashi
  • Hideki Matsumoto
  • Takeo Ohnishi
Article
  • 48 Downloads

Abstract

We investigated the effects of a protein kinase (PK) inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride), on the regulation of heat shock protein (hsp)72 gene expression in a human glioblastoma cell line (A-172) using a gel mobility-shift assay and Western blot analysis. Heat shock transcription factor 1 (HSF1) was phosphorylated immediately after heat treatment (44°C, 30 min) and the phosphorylation of HSF1 was suppressed by H-7. The increase in DNA binding ability of HSF1 to heat shock element (HSE) by heat shock was significantly suppressed by the addition of H-7 in a dose-dependent manner. Similarly, the accumulation of hsp72 by heat shock was suppressed by the addition of H-7 in a dose-dependent manner. Since H-7 is known to be a potent inhibitor of some PKs, especially calcium-dependent PK (PKC), cyclicAMP-dependent PK (PKA) and cyclicGMP-dependent PK (PKG), it is possible that the activation of HSF1 by phosphorylation and subsequent hsp72 gene expression are dependent on some of those PKs. The nature of H-7 as a non-specific inhibitor for PKs is discussed in relation to its availability for regulation of heat sensitivity of cells depending on cellular level of hsp72.

hsp72 HSF phosphorylation H-7 protein kinase inhibitor 

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Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Ken Ohnishi
    • 1
  • Xinjiang Wang
    • 1
  • Akihisa Takahashi
    • 1
  • Hideki Matsumoto
    • 1
  • Takeo Ohnishi
    • 1
  1. 1.Department of BiologyNara Medical UniversityKashihara, NaraJapan

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